Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA, 02139, USA.
Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.
Adv Healthc Mater. 2022 May;11(9):e2102411. doi: 10.1002/adhm.202102411. Epub 2021 Dec 11.
The 3D bioprinting technologies have attracted increasing attention due to their flexibility in producing architecturally relevant tissue constructs. Here, a vertical embedded extrusion bioprinting strategy using uniaxial or coaxial nozzles is presented, which allows formation of vertical structures of homogeneous or heterogeneous properties. By adjusting the bioprinting parameters, the characteristics of the bioprinted vertical patterns can be precisely controlled. Using this strategy, two proof-of-concept applications in tissue biofabrication are demonstrated. Specifically, intestinal villi and hair follicles, two liner-shaped tissues in the human body, are successfully generated with the vertical embedded bioprinting method, reconstructing some of their key structures as well as restoring partial functions in vitro. Caco-2 cells in the bioprinted intestinal villus constructs proliferated and aggregated properly, also showing functional biomarker expressions such as ZO-1 and villin. Moreover, preliminary hair follicle structures featuring keratinized human keratinocytes and spheroid-shaped human dermal papilla cells are formed after vertical bioprinting and culturing. In summary, this vertical embedded extrusion bioprinting technique harnessing a uniaxial or coaxial format will likely bring further improvements in the reconstruction of certain human tissues and organs, especially those with a linear structure, potentially leading to wide utilities in tissue engineering, tissue model engineering, and drug discovery.
3D 生物打印技术因其能够灵活地制造具有建筑相关性的组织构建体而受到越来越多的关注。在这里,提出了一种使用单轴或共轴喷嘴的垂直嵌入式挤出生物打印策略,该策略允许形成同质或异质性质的垂直结构。通过调整生物打印参数,可以精确控制生物打印垂直图案的特征。使用这种策略,在组织生物制造中展示了两个概念验证应用。具体来说,通过垂直嵌入式生物打印方法成功生成了线性组织的两种原型,即肠绒毛和毛囊,重建了它们的一些关键结构,并在体外恢复了部分功能。生物打印的肠绒毛结构中的 Caco-2 细胞增殖和聚集适当,也表现出 ZO-1 和微绒毛等功能性生物标志物的表达。此外,经过垂直生物打印和培养后,初步形成了具有角质化的人角蛋白细胞和成球形的人真皮乳头细胞的毛囊结构。总之,这种利用单轴或共轴形式的垂直嵌入式挤出生物打印技术可能会进一步改善某些人体组织和器官的重建,特别是那些具有线性结构的组织和器官,有望在组织工程、组织模型工程和药物发现中得到广泛应用。